Numerous investigations have implicated the nucleus accumbens (Acb) as a critical neural substrate that mediates the reinforcing effects of drugs of abuse such as cocaine. Previous studies in our laboratory have characterized cellular mechanisms underlying this process via electrophysiological recordings in behaving animals. These studies revealed that a subset of Acb neurons exhibit changes (increases or decreases) in firing rate synchronized to the self-administration of cocaine and are markedly influenced by drug-associated cues. Although we have shown that Acb cells are sensitive to interruption of the response-reinforcer contingency for cocaine and water reinforcement during an extinction paradigm, little is known about the effects of abstinence on Acb cell firing during cocaine self-administration. This is a critical issue since cocaine addiction in humans is typically characterized by cycles of abstinence from drug-taking and subsequent relapse. Thus, Exp. I will determine the firing properties of Acb neurons in rats well-trained to self-administer cocaine following various periods of cocaine abstinence (0, 4 and 8 weeks). Exp. II will examine the effects of cocaine abstinence on the activation of Acb neurons by cocaine-associated stimuli previously documented in our laboratory (Carelli 2000). Given that drug-associated cues are strong elicitors of 'craving' and relapse in humans, Exp. II will be directly relevant to understanding the biological basis of stimulus control in cocaine addiction. Collectively, these studies will provide important insight into the psychobiological consequences of interrupted drug access (abstinence), an important factor underlying relapse in human cocaine addicts.